Biomedical Engineering Reference
In-Depth Information
separately for heart failure. The addition of a fixed dose of isosorbide dinitrate plus
hydralazine to standard therapy for heart failure including neurohormonal blockers
was shown to be efficacious and increased survival among black patients with
advanced heart failure. The study was terminated early owing to a significantly
higher mortality rate in the placebo group than in the group treated with the drug
combination. NitroMed Inc has submitted the African American Heart Failure Trial
(A-HeFT) clinical dataset to the FDA. The product was approved by the FDA in
2005. BiDil became the first drug to be developed and marketed on the basis of a
demonstrated efficacy in black subjects and could pave the way for a generation of
individualized medicines.
Management of Hypertension
Hypertension is a common disorder affecting approximately 20% of the US popula-
tion. Care of hypertensive patients vary a lot. Ideally, individual risks must be
assessed in order for the best decision to be made as to which patients with hyper-
tension to treat and how. Assessment identifies important cardiovascular risk fac-
tors that may warrant treatment and helps to establish the absolute benefits that
patients can expect from particular treatments. The benefits of treating hypertensive
patients also vary, depending on each patient's competing risks of dying from other
than cardiovascular causes. For example, patients with multiple serious conditions,
such as end stage Alzheimer's disease, obstructive lung disease, frequent falls,
gout, and urinary incontinence, have high competing risks that may minimize or
negate the benefits of treating their hypertension. Once the decision to treat has
been made, an appropriate therapy should be selected.
Approximately, 100 medications are available for treatment in several catego-
ries: diuretics, a-blockers, b-blockers, aldosterone antagonists, angiotensin-con-
verting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, CNS active
agents, and calcium channel blockers. Each of these categories contains several
distinct drugs, which vary in their efficacy and liability to produce adverse reactions
in different patient populations. b-adrenergic antagonists are generally recom-
mended as first-line therapy, along with thiazide diuretics, for the treatment of
hypertension. However, as many as 60% of hypertensive patients do not achieve
adequate blood pressure lowering from monotherapy with b-blockers. It is plausi-
ble that genetic variation in the b-adrenergic-receptor genes accounts for some of
the observed variability in blood pressure response.
Pharmacogenomics of Diuretic Drugs
Diuretics are considered to be the first-line drugs for hypertension but their overall
efficacy is not sufficient. Many patients suffer adverse effects such as disturbances
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